Variant chr17-38543834-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_025248.3(SRCIN1):c.3406G>A(p.Ala1136Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000566 in 1,606,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SRCIN1
NM_025248.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81

Variant links:

Genes affected

SRCIN1 (HGNC:29506): (SRC kinase signaling inhibitor 1) Enables protein kinase binding activity. Involved in several processes, including regulation of dendritic spine morphogenesis; regulation of protein tyrosine kinase activity; and substrate adhesion-dependent cell spreading. Located in actin cytoskeleton and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SRCIN1 links:

SRCIN1 (HGNC:):

SRCIN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031617284).

BS2

High AC in GnomAd4 at 53 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRCIN1	NM_025248.3 linkuse as main transcript	c.3406G>A	p.Ala1136Thr	missense_variant	18/19	ENST00000617146.5	NP_079524.2	Q9C0H9-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRCIN1	ENST00000617146.5 linkuse as main transcript	c.3406G>A	p.Ala1136Thr	missense_variant	18/19	1	NM_025248.3	ENSP00000484715.1		Q9C0H9-5

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000702

AC:

AN:

242156

Hom.:

AF XY:

0.0000605

AC XY:

AN XY:

132158

show subpopulations

Gnomad AFR exome

AF:

0.00104

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000261

AC:

AN:

1454250

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

723798

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.000348

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.000540

ESP6500AA

AF:

0.00146

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000744

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.3406G>A (p.A1136T) alteration is located in exon 17 (coding exon 17) of the SRCIN1 gene. This alteration results from a G to A substitution at nucleotide position 3406, causing the alanine (A) at amino acid position 1136 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

-0.022

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.0035

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-0.93

PrimateAI

Uncertain

0.60

Sift4G

Benign

0.088

T;T

Vest4

0.41

MVP

0.068

ClinPred

0.10

GERP RS

4.9

Varity_R

0.12

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over